Growth Differentiation Factor 15 Plasma Levels and Outcome after Ischemic Stroke

Abstract

Background: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that is induced after experimental brain injury. We hypothesized that the circulating levels of GDF-15 are increased and associated with neurological outcome in patients with ischemic stroke. Methods: Serial blood samples were obtained between 6 h and 7 days after symptom onset in 57 consecutive patients with acute ischemic stroke (n = 51) or transient ischemic attack (n = 6). GDF-15 was measured by immunoradiometric assay. Neurological outcome using the modified Rankin Scale (mRS) at 7 and 90 days was classified as favorable (mRS 0 or 1) or unfavorable (mRS >1). Results: Six hours after symptom onset, GDF-15 levels were abnormally high (>1,200 ng/l) in 68% of the patients. They declined by 8% over the course of 7 days (p < 0.001). GDF-15 levels were correlated with the circulating levels of the inflammatory marker interleukin-6 and the glial protein S100 calcium binding protein B, and with carotid intima-media thickness. Ischemic stroke patients with an mRS score >1 at 7 or 90 days had higher circulating levels of GDF-15 at all preceding sampling time points compared to patients with an mRS score of 0 or 1 (p ≤ 0.002). Similarly, in a logistic regression analysis, GDF-15 levels measured between 6 h and 7 days after symptom onset were associated with mRS at 7 and 90 days. Conclusions: These data show for the first time that the circulating levels of GDF-15 are elevated and associated with neurological outcome in patients with ischemic stroke.

Change in Growth Differentiation Factor 15 Concentrations over Time Independently Predicts Mortality in Community-Dwelling Elderly Individuals

“…GDF-15 is secreted at low concentrations from most tissues but may be overexpressed in cardiomyocytes and various vascular cell types under stressful conditions (1 ). Several recent investigations have demonstrated that circulating GDF-15 concentrations are increased and independently prognostic across a wide spectrum of cardiovascular diseases, including acute and chronic coronary artery disease, congestive heart failure, and ischemic stroke (2)(3)(4)(5)(6).…”

Predicting Post-Stroke Infections and Outcome with Blood-Based Immune and Stress Markers

“…For example, elevated serum concentrations of growth differentiation factor 15 are associated with an unfavourable outcome after ischaemic stroke [56]. To date, there are only two stress markers that independently predict functional outcome and mortality: copeptin, a fragment of provasopressin, and midregional pro-atrial natriuretic peptide (MR-proANP).…”

Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke

“…10, 11 GDF-15 has also been reported to improve prediction of the risk of incident overall cardiovascular disease (CVD), heart failure, and cancer, as well as all-cause and cancer-related mortality in community-based cohorts. 12, 13 Higher GDF-15 concentrations have been noted with increasing age and in smokers, persons with diabetes, hypertension, poor kidney function, and low high-density lipoprotein cholesterol levels.…”